Abstract

Harpagophytum procumbens (H. procumbens), also known as Devil’s Claw, has been used to treat a wide range of pathological conditions, including pain, arthritis and inflammation. Inflammatory mediators, released at the site of injury, can sensitize nociceptive terminals and are responsible for allodynia and hyperalgesia. Carbon monoxide (CO), produced in a reaction catalyzed by the enzyme heme oxygenase (HO), may play a role in nociceptive processing and has also been recognized to act as a neurotransmitter or neuromodulator in the nervous system. This study was designed to investigate whether the HO/CO pathway is involved in the analgesic response of H. procumbens in carrageenan-induced hyperalgesia in rats. Mechanical allodynia and thermal hyperalgesia were evaluated by using von Frey filaments and the plantar test, respectively. The results of our experiments showed that pretreatment with the HO inhibitor ZnPP IX significantly decreased the antihyperalgesic effect produced by H. procumbens (800 mg/kg, i.p.) in carrageenan-injected rats. Consistently, the pretreatment with hemin, a HO-1 substrate, or CORM-3, a CO releasing molecule, before a low dose of H. procumbens (300 mg/kg, i.p.) induced a clear antiallodynic response in carrageenan injected rats. These results suggest the involvement of HO-1/CO system in the antiallodynic and antihyperalgesic effect of H. procumbens in carrageenan-induced inflammatory pain.

Highlights

  • Peripheral tissue injury can result in inflammatory pain, associated with a hypersensitive state due to central and peripheral mechanisms [1]

  • With this aim we evaluated the effect of protoporphyrin IX zinc (II) (ZnPP IX), hemin [20] or carbon monoxide releasing molecule 3 (CORM-3) [27] on the antinociceptive effect of

  • To investigate the role of heme oxygenase (HO)-1 activity in the antiallodynic effect of the higher dose of H. procumbens, animals were pre-treated with the HO-1 inhibitor ZnPP IX (1 mg/kg, s.c.) 30 min before the H. procumbens administration

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Summary

Introduction

Peripheral tissue injury can result in inflammatory pain, associated with a hypersensitive state due to central and peripheral mechanisms [1]. Non steroidal anti-inflammatory drugs are commonly used to reduce inflammation and pain. Endogenous carbon monoxide (CO) is a gaseous transmitter, involved in nociceptive modulation [12,13] It arises mainly from the cleavage of heme, a process catalyzed by hemeoxygenase (HO) enzyme of which there are three distinct isoforms, including the constitutive HO-2, HO-3 isoforms, and the inducible HO-1 [14]. H. procumbens in the carrageenan test was influenced by the integrity of the HO-1/CO pathway With this aim we evaluated the effect of protoporphyrin IX zinc (II) (ZnPP IX) (a specific HO-1 inhibitor), hemin (a HO-1 inducer) [20] or CORM-3 (a CO-releasing molecule) [27] on the antinociceptive effect of. H. procumbens in a model of inflammatory pain, such the carrageenan test, in rats

Mechanical Allodynia
Thermal Hyperalgesia
Animals
Carrageenan-Induced Inflammatory Pain in Rats
Experimental Design
Statistical Analysis
Full Text
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